2.02012-10-10 12:14:12 -06002015-06-03 17:25:49 -0600ECMDB23053M2MDB0034432-((2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphate2-((2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphate is an intermediate involved in thiamine diphosphate biosynthesis. Thiamine diphosphate, also known as vitamin B1, is known to play a fundamental role in energy metabolism. It is an essential cofactor for a variety of enzymes such as transketolase, pyruvate dehydrogenase, pyruvate decarboxylase, and alpha-ketoglutarate dehydrogenase. Thiamine is synthesized de novo by microorganisms, plants and some lower eukaryotes (e.g. Plasmodium), but not by higher eukaryotes, which must obtain it through their diet.(5Z)-4-Methyl-5-(2-phosphonatooxyethylidene)-2H-1,3-thiazole-2-carboxylate(5Z)-4-Methyl-5-(2-phosphonatooxyethylidene)-2H-1,3-thiazole-2-carboxylic acid(R,Z)-2-(2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphate(R,Z)-2-(2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphoric acid2-((2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphoric acidCThz*-PThiazole tautomerC7H7NO6PS264.172263.973169163(5Z)-4-methyl-5-[2-(phosphonatooxy)ethylidene]-2,5-dihydro-1,3-thiazole-2-carboxylate(5Z)-4-methyl-5-[2-(phosphonatooxy)ethylidene]-2H-1,3-thiazole-2-carboxylate[H]\C(COP([O-])([O-])=O)=C1\SC(N=C1C)C([O-])=OInChI=1S/C7H10NO6PS/c1-4-5(2-3-14-15(11,12)13)16-6(8-4)7(9)10/h2,6H,3H2,1H3,(H,9,10)(H2,11,12,13)/p-3/b5-2-PQMCQNOVNFNPFJ-DJWKRKHSSA-Klogp0.52logs-1.08solubility2.65e+01 g/llogp-0.31pka_strongest_acidic1.67pka_strongest_basic0.31iupac(5Z)-4-methyl-5-[2-(phosphonatooxy)ethylidene]-2,5-dihydro-1,3-thiazole-2-carboxylateaverage_mass264.172mono_mass263.973169163smiles[H]\C(COP([O-])([O-])=O)=C1\SC(N=C1C)C([O-])=OformulaC7H7NO6PSinchiInChI=1S/C7H10NO6PS/c1-4-5(2-3-14-15(11,12)13)16-6(8-4)7(9)10/h2,6H,3H2,1H3,(H,9,10)(H2,11,12,13)/p-3/b5-2-inchikeyPQMCQNOVNFNPFJ-DJWKRKHSSA-Kpolar_surface_area124.91refractivity66.63polarizability21.87rotatable_bond_count4acceptor_count6donor_count0physiological_charge-3formal_charge-3Vitamin B1/ThiaminePW000892MetabolicThiamin diphosphate biosynthesisPW002028MetabolicThiazole Biosynthesis IThis pathway describes only the synthesis of the thiazole moiety of thiamin. Different variations of this pathway exist, this particular pathway describes the pathway that occurs in Escherichia coli K-12 and Salmonella enterica enterica serovar Typhimurium.
The biosynthesis of the thiazole moiety is complex. In Escherichia coli it involves six proteins, the products of the thiS, thiF, thiG, thiH, thiI, and iscS genes.
The process begins when IscS, a protein that is also involved in the biosynthesis of iron-sulfur clusters, catalyzes the transfer of a sulfur atom from cysteine to a ThiI sulfur-carrier protein, generating a an S-sulfanyl-[ThiI sulfur-carrier protein].
In a parallel route, the ThiF protein activates a ThiS sulfur-carrier protein by adenylation of its carboxy terminus, generating a carboxy-adenylated-[ThiS sulfur-carrier protein]. In a second reaction, which may also be catalyzed by ThiF, the sulfur from an S-sulfanyl-[ThiI sulfur-carrier protein] is transferred to ThiS, generating a thiocarboxy-[ThiS-Protein].
The final reaction of this pathway, which is catalyzed by the ThiG protein, requires three inputs: a thiocarboxy-[ThiS-Protein], 1-deoxy-D-xylulose 5-phosphate and 2-iminoacetate.
2-iminoacetate is formed in Escherichia coli from L-tyrosine by tyrosine lyase (ThiH), which forms a complex with ThiG.
For many years the products of this reaction was assumed to be 4-methyl-5-(β-hydroxyethyl)thiazole (thiazole). However, recent work performed with the thiazole synthase from Bacillus subtilis has shown that the actual product is the thiazole tautomer 2-[(2R,5Z)-(2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate. While in Bacillus a dedicated thiazole tautomerase converts this product into a different tautomer (2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate), most of the proteobacteria lack the tautomerase. (EcoCyc)PW002041MetabolicSpecdb::NmrOneD295675Specdb::NmrOneD295676Specdb::NmrOneD295677Specdb::NmrOneD295678Specdb::NmrOneD295679Specdb::NmrOneD295680Specdb::NmrOneD295681Specdb::NmrOneD295682Specdb::NmrOneD295683Specdb::NmrOneD295684Specdb::NmrOneD295685Specdb::NmrOneD295686Specdb::NmrOneD295687Specdb::NmrOneD295688Specdb::NmrOneD295689Specdb::NmrOneD295690Specdb::NmrOneD295691Specdb::NmrOneD295692Specdb::NmrOneD295693Specdb::NmrOneD295694Specdb::MsMs27266Specdb::MsMs27267Specdb::MsMs27268Specdb::MsMs33824Specdb::MsMs33825Specdb::MsMs33826Thiamine-phosphate pyrophosphorylaseP30137THIE_ECOLIthiEhttp://ecmdb.ca/proteins/P30137.xmlThiazole synthaseP30139THIG_ECOLIthiGhttp://ecmdb.ca/proteins/P30139.xmlDehydroglycine synthaseP30140THIH_ECOLIthiHhttp://ecmdb.ca/proteins/P30140.xml1-Deoxy-D-xylulose 5-phosphate + 2-iminoacetate + thiocarboxy-adenylate-[sulfur-carrier protein ThiS] > 2-((2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphate + [sulfur-carrier protein ThiS] +2 Water4-amino-2-methyl-5-diphosphomethylpyrimidine + 2-((2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphate + 2 Hydrogen ion + 2-Methyl-4-amino-5-hydroxymethylpyrimidine diphosphate > Thiamine monophosphate + Carbon dioxide + diphosphate + Thiamine monophosphate + PyrophosphatePW_R0033362-Methyl-4-amino-5-hydroxymethylpyrimidine diphosphate + 2-((2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphate + Hydrogen ion > Carbon dioxide + Pyrophosphate + Thiamine monophosphatePW_R0059331-Deoxy-D-xylulose 5-phosphate + Dehydroglycine + a thiocarboxy-[ThiS-Protein] > 2-((2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene)ethyl phosphate + a ThiS sulfur-carrier protein +2 WaterPW_R005964